hMLH3 Inhibitors
Chemical inhibitors of hMLH3 can exert their inhibitory effects through various mechanisms which compromise the DNA replication and repair processes where hMLH3 normally functions. Camptothecin and Etoposide target essential enzymes in DNA replication; by inhibiting Topoisomerase I and II, respectively, these compounds create a scenario where the replication fork is destabilized or halted, leading to a decrease in the replication fidelity and an overload of the mismatch repair system, including hMLH3. Trifluridine, a nucleoside analog, incorporates into DNA and disrupts its normal function. This results in the formation of DNA lesions, overwhelming the repair capacity of proteins like hMLH3. Cisplatin and Mitomycin C cause crosslinking of the DNA strands, creating complex DNA damage that requires repair. The crosslinks generated can saturate hMLH3's repair capacity, leading to a functional inhibition of its activity.
Continuing with the indirect inhibition of hMLH3, PARP inhibitors such as Olaparib, Talazoparib, Rucaparib, and Veliparib increase DNA damage by preventing the repair of single-strand breaks, trapping PARP enzymes on DNA, and causing replication forks to stall. This accumulation of DNA damage indirectly inhibits hMLH3 by imposing a high demand on the mismatch repair system that it cannot meet. Methotrexate and 5-Fluorouracil interfere with nucleotide synthesis, which is crucial for DNA replication and repair. By limiting the availability of nucleotides, these drugs indirectly inhibit hMLH3 by reducing the substrates necessary for DNA synthesis, leading to replication stress where hMLH3 is active. Gemcitabine further depletes the pool of deoxynucleotides by inhibiting ribonucleotide reductase, which indirectly inhibits hMLH3 by impairing DNA synthesis and repair, creating an environment where hMLH3 cannot effectively operate. These chemical inhibitors, while not directly targeting hMLH3, lead to a functional inhibition of hMLH3 by compromising the integrity of DNA replication and repair systems, processes that are essential for the proper functioning of hMLH3.
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Items 1 to 10 of 12 total
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Camptothecin | 7689-03-4 | sc-200871 sc-200871A sc-200871B | 50 mg 250 mg 100 mg | $58.00 $186.00 $94.00 | 21 | |
Inhibits Topoisomerase I, which is necessary for DNA replication and transcription. Since hMLH3 is involved in mismatch repair during DNA replication, inhibition of Topoisomerase I can indirectly inhibit hMLH3 by preventing the DNA replication process where hMLH3 functions. | ||||||
Etoposide (VP-16) | 33419-42-0 | sc-3512B sc-3512 sc-3512A | 10 mg 100 mg 500 mg | $51.00 $231.00 $523.00 | 63 | |
Targets Topoisomerase II, another enzyme critical for DNA replication and decatenation. By inhibiting this enzyme, etoposide indirectly inhibits the function of hMLH3 by halting the DNA replication process. | ||||||
Trifluorothymidine | 70-00-8 | sc-222370 sc-222370A | 100 mg 1 g | $179.00 $500.00 | 1 | |
A nucleoside analog that incorporates into DNA and disrupts its function. Trifluridine incorporation can indirectly inhibit hMLH3 by damaging DNA and thereby reducing the substrate availability for hMLH3's mismatch repair activity. | ||||||
Cisplatin | 15663-27-1 | sc-200896 sc-200896A | 100 mg 500 mg | $138.00 $380.00 | 101 | |
Forms DNA crosslinks that the mismatch repair system, including hMLH3, recognizes and attempts to repair. Persistent crosslinks can saturate the repair system, indirectly inhibiting hMLH3's function. | ||||||
Mitomycin C | 50-07-7 | sc-3514A sc-3514 sc-3514B | 2 mg 5 mg 10 mg | $66.00 $101.00 $143.00 | 85 | |
Crosslinks DNA at the replication fork, which can indirectly inhibit hMLH3 by preventing progression of the replication machinery where hMLH3 operates. | ||||||
Olaparib | 763113-22-0 | sc-302017 sc-302017A sc-302017B | 250 mg 500 mg 1 g | $210.00 $305.00 $495.00 | 10 | |
PARP inhibitor that prevents DNA single-strand break repair. As hMLH3 is involved in the mismatch repair pathway, excessive single-strand breaks can overload the repair system, indirectly inhibiting hMLH3. | ||||||
Talazoparib | 1207456-01-6 | sc-507440 | 10 mg | $795.00 | ||
Another potent PARP inhibitor that traps PARP-DNA complexes, leading to an increase in DNA breaks and replication forks stalling, indirectly inhibiting hMLH3 by overloading the mismatch repair system. | ||||||
Rucaparib | 283173-50-2 | sc-507419 | 5 mg | $150.00 | ||
Similar to other PARP inhibitors, rucaparib increases DNA damage and can indirectly inhibit hMLH3 by enhancing the demand on the DNA repair machinery, affecting the mismatch repair process. | ||||||
Veliparib | 912444-00-9 | sc-394457A sc-394457 sc-394457B | 5 mg 10 mg 50 mg | $182.00 $275.00 $726.00 | 3 | |
A PARP inhibitor that indirectly inhibits hMLH3 by increasing replication stress and DNA damage, which may exceed the capacity of the mismatch repair system where hMLH3 functions. | ||||||
Methotrexate | 59-05-2 | sc-3507 sc-3507A | 100 mg 500 mg | $94.00 $213.00 | 33 | |
Dihydrofolate reductase inhibitor, leading to a reduction in nucleotide synthesis. This reduction can indirectly inhibit hMLH3 by limiting the availability of building blocks for DNA synthesis and repair. | ||||||